Serum elimination half-life of tamoxifen and its metabolites in patients with advanced breast cancer

Abstract

In breast cancer patients discontinuing chronic tamoxifen therapy, the serum elimination of metabolites X, Y and E paralleled that of tamoxifen, whereas that of metabolite Z did not. The serum elimination of tamoxifen and metabolites X and B was increased by amino-glutethimide treatment, whereas that of metabolites Z, Y, and E was not.

Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens

“…In a separate study with patients under tamoxifen therapy, shorter mean serum half-lives were determined for tamoxifen (3.0 ± 1.5 days) and N-desmethyl-tamoxifen (6.0 ± 1.2 days) in the presence of aminoglutethimide compared with treatment with tamoxifen alone. However, the corresponding values of N-didesmethyl-tamoxifen, deaminohydroxy-tamoxifen and 4'-hydroxy-tamoxifen were 16.1 ± 7.6days, 8.4 ± 2.3 days and 7.2 ± 1.3 days, respectively, and thus remained nearly unchanged when amino glutethimide was co-administered (DE Vos et al 1992).…”

“…The mean terminal half-life of tamoxifen was 9.6 ± 2.5 days and was similar to that of N-desmethyl-tamoxifen (10.3 ± 2.9 days), deaminohydroxy-tamoxifen (11.9 ± 4.6days) and 4'-hydroxy-tamoxifen (10.3 ± 3.3 days), but was shorter than that of N-didesmethyl-tamoxifen (17.5 ± 9.6 days). The concentrations of 4-hydroxy-tamoxifen were low and, therefore, the halflife of this metabolite could not be evaluated (DE VOS et al 1992). After single administration, a similar mean terminal half-life of 8.75 days was determined for tamoxifen in healthy postmenopausal women (FUCHS et al 1996).…”

Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry

“…Other studies have failed to demonstrate a relationship between serum levels of tamoxifen and major metabolites and de novo tamoxifen resistance [54,55]. Because tamoxifen and its metabolites are primarily excreted by the biliary route, only small quantities of these compounds can be observed in urine (only approximately 20% of tamoxifen metabolites are excreted into urine [21], and the relationships between serum and urine metabolite profiles are not well studied. Nonetheless, we have observed several interesting correlations between patients' clinical characteristics and urinary tamoxifen metabolite profiles.…”

“…Many efforts have been made to study tamoxifen biotransformation [1,[18][19][20][21][22][23]. Some of the known metabolites are listed in Table 1.…”

The novel anti-oestrogen idoxifene inhibits the growth of human MCF-7 breast cancer xenografts and reduces the frequency of acquired anti-oestrogen resistance

“…In vivo idoxifene was shown to have a significantly longer terminal half-life than tamoxifen in the rat (Haynes et al, 1991). In a recent phase I study in women with advanced breast cancer (Coombes et al, 1995), the terminal half-life of idoxifene was 3 weeks compared with a known half-life for tamoxifen of 7 days (DeVos et al, 1992). In addition, the antagonist/agonist profile for idoxifene appears favourable to that for tamoxifen.…”